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Publicatie Doce=Pred studie DUOS

Tot november 2017 werd binnen DUOS de studie Doce=Pred uitgevoerd naar de invloed van prednison op de AUC van docetaxel vergeleken met de AUC van docetaxel alleen bij patiënten met castratie-resistent en hormoon-sensitief gemetastaseerd prostaatcarcinoom. Het secondair doel van deze studie was onderzoek naar incidentie en ernst van bijwerkingen tijdens behandeling met docetaxel in aan- en afwezigheid van prednison. Hier treft u een pdf met een samenvatting van deze studie.  De studie is nu officieel gepubliceerd in de Britsh Journal of  Clinical Pharmacology.

Effects of prednisone on docetaxel pharmacokinetics in men with metastatic prostate cancer: A randomized drug–drug interaction study

Abstract

Aims

Docetaxel has been approved for the treatment of metastatic prostate cancer in combination with prednisone. Since prednisone is known to induce the cytochrome P450 iso‐enzyme CYP3A4, which is the main metabolizing enzyme of docetaxel in the liver, a potential drug–drug interaction may occur. In this prospective randomized pharmacokinetic cross‐over study we investigated docetaxel exposure with concomitant prednisone, compared to docetaxel monotherapy in men with metastatic prostate cancer.

Methods

Patients scheduled to receive at least 6 cycles of docetaxel (75 mg/m2) and who gave written informed consent were randomized to receive either the 1st 3 cycles, or the last 3 consecutive cycles with prednisone (twice daily 5 mg). Pharmacokinetic blood sampling was performed during cycle 3 and cycle 6. Primary endpoint was difference in docetaxel exposure, calculated as area under the curve (AUC0inf) and analysed by means of a linear mixed model. Given the cross‐over design the study was powered on 18 patients to answer the primary, pharmacokinetic, endpoint.

Results

Eighteen evaluable patients were included in the trial. Docetaxel concentration with concomitant prednisone (AUC0inf 2784 ng*h/mL, 95% confidence interval 2436–3183 ng*h/mL) was similar to the concentration of docetaxel monotherapy (AUC0inf2647 ng*h/mL, 95% confidence interval 2377–2949 ng*h/mL). Exploratory analysis showed no toxicity differences between docetaxel monotherapy and docetaxel cycles with prednisone.

Conclusion

No significant difference in docetaxel concentrations was observed. In addition, we found similar toxicity profiles in absence and presence of prednisone. Therefore, from a pharmacokinetic point of view, docetaxel may be administrated with or without prednisone.

 

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